Modulation der Insulinwirkung im Gehirn durch Nahrungsfette
Final Report Abstract
Fat and physical inactivity are the most evident factors in the pathogenesis of obesity, and fat quality seems to play a crucial role for measures of glucose homeostasis. However, the impact of dietary fat quality on brain function, behavior, and sleep is basically unknown. In this project, human and mice studies were combined to investigate acute and long term effects of fat intake on brain functions. In humans, a functional magnetic resonance imaging study revealed differential homeostatic and gustatory effects dependent of intake of a high or low fat meal. The hypothalamus, representing the homeostatic control center of the brain, showed a pronounced decrease of cerebral blood flow (CBF) after the ingestion of the high fat yoghurt and the corresponding CBF change correlated positively with the insulin change. Furthermore, the activity of the insular cortex, the primary gustatory cortex, showed pronounced activation in the low fat condition. The CBF change of both regions correlated positively in the high fat condition. For the investigation of long term effects, we investigated the effect of a 3-month fat intervention in humans and mice. The mice were fed a diet supplemented with either monounsaturated fatty acids (MUFAs) or saturated fatty acids (SFAs) and their impact on glucose homeostasis, locomotion, brain activity, and sleep behavior was evaluated. MUFAs and SFAs led to a significant increase in fat mass but only feeding of SFAs was accompanied by glucose intolerance in mice. Radiotelemetry revealed a significant decrease in cortical activity in SFA-mice whereas MUFAs even improved activity. SFAs decreased wakefulness and increased non–rapid eye movement sleep. An intracerebroventricular application of insulin promoted locomotor activity in MUFA-fed mice, whereas SFA-mice were resistant. In humans, SFA-enriched diet led to a decrease in hippocampal and cortical activity determined by functional magnetic resonance imaging techniques. Together, dietary intake of MUFAs promoted insulin action in the brain with its beneficial effects for cortical activity, locomotion, and sleep, whereas a comparable intake of SFAs acted as a negative modulator of brain activity in mice and humans. The overall conclusion of this project is that fat has an important impact on brain functions, locomotion and sleep. Different types and amounts of fat highly influence neural functions in humans and animals showing the importance of an even more critical examination of nutrient ingredients.
Publications
- (2012) Fat intake modulates cerebral blood flow in homeostatic and gustatory brain areas in humans. Am J Clin Nutr 95:1342-1349
Frank S, Linder K, Kullmann S, Heni M, Ketterer C, Cavusoglu M, Krzeminski A, Fritsche A, Haring HU, Preissl H, Hinrichs J, Veit R
(See online at https://doi.org/10.3945/ajcn.111.031492) - (2012) Monounsaturated fatty acids prevent the aversive effects of obesity on locomotion, brain activity, and sleep behavior. Diabetes 61:1669-1679
Sartorius T, Ketterer C, Kullmann S, Balzer M, Rotermund C, Binder S, Hallschmid M, Machann J, Schick F, Somoza V, Preissl H, Fritsche A, Haring HU, Hennige AM
(See online at https://doi.org/10.2337/db11-1521)
